Abstract

The distal nephron is a heterogeneous part of the nephron composed by six different cell types forming the epithelium of the distal convolute (DCT), connecting (CNT) and collecting duct (CD). To dissect the function of these cells, knock out models specific for their unique cell marker have been created.
However, since this part of the nephron develops at the border between the ureteric bud and the metanephric mesenchyme, the specificity of the single cell-markers has been recently questioned.
Here, by mapping the fate of the AQP2, NCC-positive cells using transgenic mouse lines expressing the YFP fluorescent marker, we showed that the origin of the distal nephron is extremely composite. Indeed, AQP2 expressing precursors results to give rise, not only, to the principal cells, but also, to some of the A- and B-type intercalated cells and even to cells of the DCT. On the other side, some principal cells and B-type intercalated cells can develop from NCC expressing precursors.
In conclusion, these results demonstrate that the origin of different cell types in the distal nephron is not as clearly defined as originally thought. Importantly, they highlight the fact that knocking out a gene encoding for a selective functional marker in the adult life does not guarantee cell specificity during the overall kidney development. Tools allowing not only cell-specific but also time-controlled recombination will be useful in this sense.